During the past few years data have accumulated suggesting the involvement of prolactin (PRL) in rapid eye movement sleep (REMS) regulation. Pituitary PRL secretion seems to be, at least in part, sleep-dependent. PRL is also found in the central nervous system. PRL-containing neurons in the hypothalamus project to various structures in the brain. Systemic injection of PRL promotes REMS in rats, cats and rabbits. Intracerebroventricular injection of PRL enhances REMS in rats. Stimulation of endogenous PRL secretion by vasoactive intestinal peptide (VIP) also promotes REMS. Immunoneutralization of blood-borne PRL slightly reduces REMS. Various observations (hypoprolactinemic and hyperprolactinemic rats) indicate that PRL may act on REMS via modulating the diurnal rhythms of REMS. It is likely that hypothalamic PRL is more important for sleep regulation than circulating PRL. Hypothalamic PRL is likely involved in the mediation of the REMS-promoting activity of VIP. We conclude that PRL has a role in REMS regulation.